The fate of leukocytes in a tissue microenvironment is strongly influenced by up- or down-regulation of cell-surface receptor expression, and subsequent interaction of the receptors with their ligands. These ligands include a wide range of agents secreted at the sites and the components of the extracellular matrix (ECM). Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase whose ligand is collagen. We recently detected, for the first time, that peripheral blood mononuclear cells and neutrophils were induced to express DDR1. Functionally, overexpression of the DDR1a isoform in the human monocytic leukemic cell line, THP-1, increased adherence and marked pseudopod formation on collagen-coated plates in a 1-integrin independent manner, and promoted the migration through three-dimensional collagen lattices. Consequently, we have proposed that the interaction of DDR1a with collagen of the ECM results in a requisite intracellular signaling that enables leukocytes to migrate in a tissue microenvironment and participate in host defense.